There are many continuous and complex interactions occuring between cell surfaces and soluble, circulating immunoglobulins in the intact animal. One very important part of such molecular social behavior is the monitoring of macromolecular integrity. Although there is virtually nothing known about how the monitoring process(es) work, it is well established that the body is capable of recognizing aged or damaged molecules and of eliminating them. Thus, molecular catabolism is a fundamental aspect of normal immunoglobulin homeostasis, and catabolic mechanisms are intricately involved in neoplastic, infectious and autoimmune disorders. Studies of the rates of macromolecular metabolism have important bearing on the role of the immune response in the aging process. Measurements of serum antibody levels provide indications of the rates of synthesis, patterns of distribution and rates of catabolism of total immunoglobulin populations--and thus the immune status of the host. We are evaluating antibody metabolism (synthesis as well as clearance from the circulatory system) at the whole-body level during aging. Studies are focusing on selected murine model systems with particular emphasis on the catabolic rates (and mechanisms responsible) of IgG subclasses, aglycosyl-antibodies and idiopathic paraproteins (homogeneous immunoglobulin-related molecules). In addition to determining the relative degree of functioning of catabolic mechanisms during aging, methods are being developed for assessing bone marrow proliferative capacity and for accurately identifying and characterizing circulating paraproteins in aged animals. The objectives of these studies are to understand the functioning of clearance processes during aging, how these processes are involved in the phenomenon of idiopathic paraproteinemia and the extent to which altered antibody metabolism may be involved in the aging process and in hypogammaglobulinemia associated with monoclonal gammonpatheis.